ASSOCIATION BETWEEN HLA AND ISLET-CELL ANTIBODIES IN DIABETIC-PATIENTS WITH A MITOCHONDRIAL-DNA MUTATION AT BASE-PAIR-3243

Islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxy lase (GAD) and HLA genotypes were examined in 31 patients with diabete s and a mitochondrial gene mutation located at base pair 3243 (mtDNA 3 243 mutation), ICA was detected in 42 % (13/31) of these patients comp ared to 0 of 90 among healthy control subjects. The ICA showed a ''non -restricted'' pattern of staining in all 13 ICA-positive patients. In a sensitive radioligand assay only 2 of 31 (6 %) diabetic patients wit h the mutation were positive for both GAD65 autoantibodies and ICA, wh ile the remaining 29 patients were GAD65 antibody negative, The ICA-po sit ive patients had an increased frequency of the HLA-DQA10301 allel e compared to control subjects (p < 0.05). Of the diabetic patients wi th the mutation 45 % (14/31) had progressive clinical course of beta-c ell failure. These results indicate that patients With an mtDNA 3243 m utation may develop islet autoimmunity associated with ICA and GAD aut oantibodies. We hypothesize that the presence of HLA-DQA10301 in indi viduals with the mtDNA 3243 mutation increases the risk for diabetes a nd associated autoantibodies against islet cell antigens.